Prolactin receptor expression in human testis and accessory tissues: localization and function.

Experimental studies in animals have established prolactin (PRL) as a progonadal hormone that promotes the function of the testis and reproductive accessory glands. The present study investigated the localization of PRL receptor (PRL-R) expression in the human testis and accessory tissues. Expression of PRL-R was identified in human testis and vas deferens by RT-PCR, and further localized by immunohistochemistry to the Leydig cells and differentiating germ cells of the testis (developmental stages extending from pachytene spermatocytes to elongating spermatids). Positive staining for PRL-R was also clearly evident in the epithelium of vas deferens, epididymis, prostate and seminal vesicles. Functional activation of PRL-R was demonstrated in fresh samples of vas deferens collected at vasectomy by examination of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAP (mitogen-activated protein) kinase ERK (extracellular signal-regulated kinase) signalling pathways. Within the vas deferens, PRL induced rapid tyrosine phosphorylation of JAK 2 and STAT 5 (after 10 and 20 min respectively), and tyrosine and threonine phosphorylation of ERK 1 and 2 (after 5 min). The demonstration of function and localization of PRL-R presented here suggests multiple roles for PRL in the human male reproductive tract.

A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range.

Activational effects of testosterone on cognitive function in men.

OBJECTIVES: The effect of testosterone (T) on sexual function in men is well established. However, less is known about its effects on cognitive function. The aim of this study is to investigate the relationship between T levels and sex-typed cognitive abilities in both eugonadal and hypogonadal men. DESIGN: A single-blind placebo-controlled design was employed in this study. METHODS: Thirty healthy eugonadal men and seven hypogonadal men participated in the study. Eugonadal men were randomised into one of two treatment regimens: (1) active group--receiving 200 mg of T enanthate i.m. weekly for 8 weeks (raising T levels into the supraphysiological range) or (2) placebo group--receiving 200 mg of sodium chloride i.m. weekly for 8 weeks. The hypogonadal group received the physiological replacement dose of 200 mg T enanthate i.m. bi-weekly for 8 weeks. All groups underwent a battery of neuropsychological tests and had circulating T measured at baseline, and at weeks 4 and 8 during treatment. RESULTS: A significant time by group interaction effect was found in the measure of spatial ability (i.e., block design test) indicating that the active group's performance declined significantly at week 4, compared to placebo group (F(4,64)=3.78, P<0.01). Conversely, the active group performed significantly better than the placebo group in the measure of verbal fluency (i.e., the Controlled Oral Word Association Test) at week 4 (F(4,64)=2.54, P<0.05). No significant changes were found on any of the other tests. Generally, the hypogonadal group performed less well than the eugonadal groups on all tests. CONCLUSIONS: These results offer support to the notion that increased T has a differential effect on cognitive function, inhibiting spatial abilities while improving verbal fluency in eugonadal men.

Male contraception: prospects for the new millennium.

Effective regulation of human fertility has global consequences in terms of resource depletion, pollution and poverty. Current family planning services predominantly target a female clientele with few significant developments in male fertility regulation for over a century. The last two decades have witnessed a gathering interest, initially from the scientific community, and laterally from industry, in the development of safe, reliable, reversible methods of contraception for men. This review summarises the methods of male fertility regulation which are currently available and critically examines the published data on novel developments in male hormonal contraception which offer the potential of improved contraceptive choice for all in new millennium.

Effect of calcium antagonists on endothelin-induced contraction of isolated human resistance arteries: differences related to site of origin.

Small resistance arteries were isolated from human subcutaneous fat and omentum and studied using a myograph. Endothelin-1 induced a concentration-dependent contraction in both type of arteries. In subcutaneous arteries preincubation with calcium antagonists partially inhibited responses to endothelin-1. The effectiveness of the calcium antagonists was nisoldipine > nimodipine > verapamil = flunarizine > diltiazem. In omental arteries nimodipine and diltiazem had no significant effect on endothelin-1-induced contraction and removal of extracellular calcium also had little effect on responses to endothelin-1. The role of influx of extracellular calcium through voltage operated calcium channels in endothelin-1-induced contraction appear to differ between subcutaneous and omental resistance arteries.

Human vascular responses to endothelin-1: observations in vivo and in vitro.

These studies have investigated the effect of endothelin-1 (ET-1) on human resistance vasculature in vivo and in vitro. ET-1 was infused via the brachial artery and forearm blood flow (FBF) measured by venous occlusion plethysmography. Isolated resistance vessels were studied in a myograph. ET-1 (10 pmol-10 nmol/min, i.a.) reduced forearm blood flow. Endothelin-1-induced forearm vasoconstriction was slow to recover following washout. ET-1 (10 pM-10 nM) contracted isolated human subcutaneous and omental resistance vessels. Contractile responses to ET-1 were sustained and washout recovery was slow. Responses to ET-1 displayed marked tachyphylaxis. Calcium channel blockers and removal of extracellular calcium failed to completely abolish responses to ET-1 in vitro.

Size and site-dependent heterogeneity of human vascular responses in vitro.

Ring segments of splanchnic, peripheral, coronary, pulmonary and uterine conduit arteries obtained during surgery were studied in tissue baths. Resistance arteries dissected from various sites were studied in a myograph. Both conduit and resistance vessels contracted in response to the alpha 1-agonist phenylephrine (10(-7) to 10(-4) mol/l), an effect that was antagonized by the alpha 1-antagonist doxazosin (10(-8) to 10(-6) mol/l). However, the alpha 2-agonists BHT 933 (10(-7) to 10(-4) mol/l) and UK 14304 (10(-7) to 10(-4) mol/l) only contracted the resistance vessels and not the conduit arteries. The response to BHT 933 was competitively antagonized by the alpha 2-antagonist yohimbine (3.10(-8) to 3.10(-7) mol/l) and the magnitude of the contractile response was inversely related to vessel size. Similarly, neuropeptide Y (10(-9) to 10(-6) mol/l) contracted only the resistance vessels, and induced marked tachyphylaxis. Atrial natriuretic peptide (ANP; 10(-8) to 10(-6) mol/l) produced concentration-dependent relaxation in all conduit arteries studied, being ineffective in resistance arteries from subcutaneous or omental sites, but relaxed those from renal tissue and skeletal muscle. Calcitonin gene-related peptide (10(-8) to 10(-6) mol/l) and vasoactive intestinal peptide (10(-9) to 10(-6) mol/l) relaxed both conduit and resistance arteries. This response was dependent on the integrity of the endothelium in the systemic conduit but not the resistance vessels. These results indicate that the receptors for adrenergic agonists and vasoactive peptides are varyingly distributed throughout the human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)